飞行时间质谱法检测干扰素调节因子6单核苷酸多态性的研究

目的研究基质辅助激光解吸电离飞行时间质谱（matrix assisted laser desorption ionization time of flightmass spectrometry,MALDI-TOF-MS）技术检测唇腭裂相关基因干扰素调节因子6（interferon regulatory factor 6,IRF6）单核苷酸多态性（single nucleotide polymorphisms,SNPs）的效果。方法样本来自201名健康志愿者,利用PCR扩增出IRF6基因含rs2235371和rs642961位点片段作为模板,并以位点特异引物进行单碱基延伸反应,产物纯化后利用MALDI-TOF-MS技术对rs2235371和rs642961的多态性进行检测。结果 201名健康志愿者IRF6基因rs2235371和rs642961位点的基因型和等位基因的分布频率与HAPMAP基因库中中国人群同一基因位点的分布频率相近。结论 MALDI-TOF-MS技术是一种高通量快速检测基因SNPs的方法。     

下三角瓣法单侧唇裂修复术后唇鼻部形态的测量研究

对８２例单侧唇裂经下三角瓣法单侧唇裂修复的唇腭裂患者，术后平均５年唇鼻形态的测量，进行对称性分析研究，结果表明：①单侧唇裂患者术后双侧上唇部的形态大体比例均衡，患侧唇高不会出现过长或过短的现象；②患侧伤口张力的大小对上唇高度的发育有一定的影响；③下三角瓣术式中，三角瓣基底宽的设计不能小于唇高差，对Ⅲ度唇裂可适当增加０．５～１．０ｍｍ；④下三角瓣法存在一期手术后遗留患侧鼻孔较大的弱点。     

2011—2015年广东省唇腭裂流行状况分析

目的了解2011—2015年广东省唇腭裂流行状况。 方法以2011—2015年在广东省出生缺陷监测体系内58家医院分娩的围产儿（孕28周至出生后7天）及孕产妇为研究对象,描述性分析广东省唇腭裂分布及类型特征,使用卡方检验、有序分类回归,构成比进行统计学分析。 结果符合纳入标准的围产儿1 203 800例,检出唇腭裂1664例,检出率为13.83/万;广东省内揭阳市检出率最高为21.30/万,湛江市检出率最低为7.78/万。2011—2015年逐年检出率分别为15.81/万、14.00/万、9.02/万、15.81/万、11.00/万,各年份间无明显趋势性;总唇腭裂检出率在4月最高和9月最低,差异无统计学意义（χ²= 128.34,P= 0.403）。孕产妇年龄分层中,>35岁年龄组和<20岁年龄组检出率较高,分别为23.86/万和17.73/万;男性围产儿检出率为16.45/万,女性围产儿的检出率为12.40/万,性别间总唇腭裂的检出率差异有统计学意义（χ²= 32.74,P<0.0001）,唇腭裂类型在不同围产儿性别间的分布其差异有统计学意义（χ²= 52.78,P= 0.0012）。唇裂、腭裂、唇裂合并腭裂的构成比分别为27.94%、25.54%、46.51%。 结论加强唇腭裂区域防控措施,进一步研究唇腭裂性别差异的影响因素,普及优生优育及出生缺陷防控相关健康教育以减少出生缺陷的发生。     

不完全性腭裂修复术后患者替牙期的颅面特征初探

目的比较不完全性腭裂患者修复术后与健康儿童替牙期颅面形态的差别，进一步了解不完全性腭裂患者的颅面特征。方法选择20例不完全性腭裂修复术后，处于替牙期的患者作为腭裂组，年龄7～11岁；选择年龄、性别匹配的非腭裂健康儿童35名作为对照组。对两组研究对象的头颅侧位X线片进行X线头影测量对比分析。结果腭裂组全颅底长、上颌长、下颌有效长度分别为86．48mm、44．79mm、65．45mm，对照组分别为91．27mm、48．84mm、70．49mm，差异均有统计学意义（P〈0．001）。结论不完全性腭裂患者颅面部发育不足，呈Ⅲ类骨面型。     

干扰素调节因子-6基因多态性与非综合征型唇腭裂的相关性研究

20世纪80年代后期以来,学者们陆续报道了10～20个与非综合征型唇腭裂有关的易感基因和位点,其中干扰素调节因子-6（IRF-6）基因是迄今发现的最有价值的与非综合征型唇腭裂发病相关的基因之一。本文就IRF-6基因的结构和功能、IRF-6基因的多态性及其与非综合征型唇腭裂的相关性研究作一综述。     

Cephalometric evaluation of rapid and slow maxillary expansion in patients with BCLP: Secondary data analysis from a randomized clinical trial

Objective:To compare the dentoskeletal effects of rapid (RME) and slow (SME) maxillary expansion in patients with bilateral complete cleft lip and palate (BCLP).Materials and Methods:This was a secondary analysis of a previous randomized controlled trial (RCT). Forty-six patients (34 male, 12 female) with BCLP and posterior crossbite (mean age of 9.2 years) were randomly assigned to two study groups. Group RME comprised subjects treated with Haas/Hyrax expander. Group SME included patients treated with quad-helix appliance. Cone-beam computed tomography (CBCT) was performed before expansion (T1) and after appliance removal at the end of a 6-month retention period (T2) for a previous RCT that compared the transverse skeletal effects of RME and SME. CBCT-derived cephalometric images were generated and cephalometric analysis was performed using Dolphin Imaging Software (Chatsworth, Calif). Intergroup comparisons were performed using t tests (P < .05).Results:Baseline forms were similar between groups. No significant differences between RME and SME groups were found.Conclusions:Rapid and slow maxillary expansion produced similar sagittal and vertical changes in patients with BCLP. Both Haas/Hyrax and quad-helix appliances can be used in patients with vertical facial pattern. Clinical relevance: RME and SME can be equally indicated in the treatment of maxillary arch constriction in patients with BCLP.     

唇腭裂患者鼻唇侧貌协调性评价的研究

目的:分析唇腭裂患者鼻尖突度、鼻上唇协调性、上下唇协调性主观评价与客观评价之间的相关性;并分析鼻突角、鼻唇角、唇间角在整体评价中的敏感程度.方法:选取患者的150张标准侧面相进行评价.主观评价包括局部评价(鼻尖突度、鼻上唇协调性、上下唇协调性)及整体评价.局部评价采用VAS评分系统,整体评价采用等级评分系统;客观评价采...     

One-stage cleft repair outcome at age 6- to 18-years -- a comparison to the Eurocleft study data

The optimisation of the relation between quality of outcome and burden of care is difficult in the treatment of cleft lip and palate. We analysed long-term outcome after one-stage repair of clefts to assess the benefits and limitations of this form of treatment. Thirty-three patients aged 6-18 years who had had lip repair, two-flap palatoplasty, and corticocancellous alveolar bone grafts at 6 months of age were divided into three age groups (6-11, 12-14, and 15-18 years) and compared with mean outcome data from the Eurocleft centres and with cephalometric standards of healthy people. Fifteen of the 33 patients were assessed for nasalance. Maxillary protrusion (SNA) and intermaxillary relation (ANB) in the one-stage groups differed significantly from those of healthy people, but not from corresponding means in the Eurocleft study. In 61% the Bergland score for alveolar ossification was grade I or II, and in 15% it was grade III; 24% had secondary alveolar bone grafting. No palatal fistulas occurred and nasalance did not differ significantly from that of healthy controls. As each patient generally had a primary operation and one secondary procedure, they benefited from half the number of surgical steps of multistage procedures. However, one-stage procedures led to significant disturbance in growth, but the degree of this was similar to mean values of multistage procedures in the Eurocleft study. Primary alveolar bone grafting led to inconsistent alveolar ossification and was suspected to interfere with anterior maxillary growth so it has been abandoned.     

Three-dimensional analyses of nasolabial forms and upper lip surface symmetry after primary lip repair in patients with complete unilateral cleft lip and palate

Purpose

To analyze three-dimensional (3D) nasolabial forms and upper lip surface symmetry after primary lip repair in children with unilateral cleft lip and palate (UCLP).

干扰素调节因子6基因致病的Van der Woude综合征的家系调查和遗传特点分析

目的 探讨中国人Van der Woude综合征（VWS）的临床表型及遗传学特点。方法 先证者法收集14个VWS家系并进行口腔专科检查、家系调查及基因突变分析,分析不同VWS家系个体或同一家系不同个体的临床表型,绘制家系图谱,明确遗传方式及致病基因,计算表型分布频率和表型基因频率。结果 VWS家系基本符合常染色体显性遗传特征,患者多数表现为典型的VWS,致病基因为干扰素调节因子6（IRF6）。VWS表型分布频率为：唇瘘91.9%,唇腭裂73.0%,牙畸形8.1%。不同家系个体和同一家系的不同个体临床表型存在明显差异。结论 收集的家系均为常染色体显性遗传,表现度变异大。中国人群VWS致病基因为IRF6,为Ⅰ型VWS。     

上颌-鼻软骨整形矫治器在婴儿双侧完全性唇腭裂术前正畸中的应用

目的 探讨上颌-鼻软骨整形矫治器在婴儿期双侧完全性唇腭裂术前正畸中的应用价值.方法 对50例双侧唇腭裂患儿,随机分为试验组(n＝30)与对照组(n＝20),试验组于出生10 d～1个月内进行上颌-鼻软骨整形矫治器矫治,对照组均不做术前正畸.两组患儿正畸治疗前(T1)后(T2)对比上唇裂隙、上前牙槽突裂隙关闭程度,对比两组唇腭裂联合整复术后3个月鼻翼外观满意度,作出评价.结果 两组患儿T1、T2两侧上唇裂隙及牙槽突裂隙宽度差别无统计学意义(P＞0.05).患儿术后鼻翼外观满意度试验组87%,高于对照组60%(P＜0.05).结论 该治疗有效减少上唇及上颌骨牙槽突的裂隙宽度,改善鼻外观,达到降低手术难度,增加手术效果的目的.     

Non-syndromic cleft lip with or without cleft palate in Asian populations: Association analysis on three gene polymorphisms of the folate pathway

ObjectiveOrofacial clefts (OFCs) are one of the most common birth defects in humans. They are the subject of a number of investigations aimed at elucidating the bases of their complex mode of inheritance involving both genetic and environmental factors. Genes belonging to the folate pathway have been among the most studied. The aim of the investigation was to replicate previous studies reporting evidence of association between polymorphisms of folate related genes and the occurrence of non-syndromic cleft lip with or without cleft palate (NSCL/P), using three independent samples of different ancestry: from Tibet, Bangladesh and Iran, respectively.DesignSpecifically, the polymorphisms rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were tested.ResultsA decreased risk of NSCL/P was observed in patients presenting the C677T variant at MTHFR gene (relative risk for heterozygotes = 0.53; 95% confidence interval [C.I.] = 0.32–0.87). The investigated polymorphisms mapping at TCN2 and CBS genes did not provide any evidence of association.ConclusionOverall, these results indicate that NSCL/P risk factors differ among populations and confirm the importance of testing putative susceptibility variants in different genetic backgrounds.     

中国人群非综合征性唇腭裂患者IRF6基因突变检测

目的 探讨干扰素调节因子6(interferon regulatory factor 6, IRF6) 在非综合征性唇腭裂(non-sydromic cleft lip and/or cleft palate,NSCL/P)患者中的突变情况。方法：收集119例NSCL/P患者及288名健康人对照样本的外周血血样并提取DNA。在IRF6基因的全部外显子分别设计引物,PCR扩增其序列,通过测序找出IRF6基因突变,并将这些突变在对照样本中进行验证。结果：共发现5种在正常人中没有的突变,其中4种是新发现的突变。结论：IRF6基因突变在中国人群中参与了非综合征唇腭裂疾病的发生。     

恒牙列早期唇腭裂修复术后患者下颌骨位置与形态的测量研究

目的：研究唇腭裂修复术对下颌骨形态和位置的影响。方法：选取21例非唇腭裂患者（非裂患者）作为A组（男10例,女11例,平均年龄13.10岁）,19例单侧唇腭裂伴牙槽突裂患者作为B组（男11例,女8例,平均年龄11.57岁）,17例双侧唇腭裂伴牙槽突裂患者作为C组（男10例,女7例,平均年龄12.50岁）。在正畸治疗前进行头影测量,分析下颌骨的形态和位置,使用SPSS17.0软件包对3组患者的测量数据进行独立样本t检验。结果：单侧唇腭裂患者与非裂患者在ANSMe、SNB、BaNPog和CoGo-MP存在显著差异（P〈0.05）,在CoGo、GoGn、CoGn、SGo和NMe也存在显著差异（P〈0.01）。双侧唇腭裂患者与非裂患者在GoGn和SN-MP存在显著差异（P〈0.05）,在SNB和CoGo-MP也存在显著差异（P〈0.01）。结论：唇腭裂修复术对下颌骨生长发育的影响主要表现在下颌骨矢状向位置偏后,下颌体长度减小,下颌支高度降低以及下颌骨向后、向下旋转。     

中国西部人群IRF6基因SNPs与非综合征型唇腭裂相关性的研究

目的:探讨干扰素调节因子6 (IRF6) 基因rs2013162 和 rs2235375位点单核苷酸多态性(SNPs)与非综合征型唇腭裂的相关性.方法:收集病例组非综合征型唇腭裂患儿332 例,患者父亲243 例,患者母亲289 例,完整的核心家庭206个.对照组收集正常新生儿174 例.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测IRF6基因这2 个多态位点基因型,进行病例对照和传递不平衡(TDT)分析.结果:在中国西部人群中,与正常对照组比较,唇腭裂组rs2235375位点的基因型和等位基因的频率存在统计学差异(均P<0.01).运用传递不平衡研究发现IRF6基因rs2235375位点的G等位基因在唇腭裂患者中存在过传递(P<0.01).有5 种单倍型组合显示有传递不平衡.结论:在中国西部人群中IRF6基因多态性与非综合征型唇腭裂的发生存在强的相关性.     

Postoperative lip and nose forms following primary bilateral cleft lip repair selecting one/two stage surgery in comparison to those of healthy children

PurposeTo analyze the short-term outcomes for the lip and nasal forms after primary treatment following our surgical strategy for bilateral cleft lip with/without palate (BCL ± P) repair selecting one- or two-stage surgery at Kagoshima University Hospital.Patients and methodsTwenty-one patients with BCL ± P were treated and followed up over 1 year (1–6 years). Patients underwent primary lip repair by one- or two-stage surgery depending on the prolabium height, medial-upward advancement of nasolabial components, and vestibular expansion using two cleft margin flaps. The postoperative lip and nasal forms were longitudinally measured using serial color photographs and were compared to those of 18 age- and sex-matched healthy Japanese children.ResultsPostoperative lip form showed the upper lip height and vermilion mucosal height were significantly increased compared with the preoperative values. The vermilion/cutaneous lip height ratio was improved to the same level as that of controls at 3 years of age. Symmetry of lip and nasal forms was successfully achieved postoperatively, but the nasal height was still smaller than that of controls.ConclusionsOur surgical management strategy for BCL ± P will provide well-balanced and symmetrical lip and nasal forms, except for the nasal height, without damaging an infant's prolabium.     

BMP4、TGF-β3基因多态性与环境暴露在非综合征性唇腭裂发生中的交互作用

目的 探讨环境暴露因素、骨形态生成蛋白4(BMP4)基因、转化生长因子β3(transforming growth factor beta-3,TGF-β3)基因之间的交互作用在非综合征性唇腭裂(nonsyndromic cleft lip and cleft palate,NSCLP)发生中的可能作用.方法 通过问卷调查获取环境暴露资料.用聚合酶链反应(PCR)-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术对对照组(200例)和NSCLP组(200例)各基因位点的多态性进行检测.采用多因子降维法(multifactor djmensionality reduction,MDR)分析基因之间、基因与环境之间的交互作用关系,并对筛选的交互作用关系用Logistic回归进行验证.结果 BMP4 T538C、TGF-β3 C641A和TGF-β3G15572-三个单核苷酸多态性(single nucleotide polymorphism,SNP)位点间的交互作用与NSCLP的发生无关联.基因与环境交互作用分析发现,BMP4 T538C与母亲妊娠早期被动吸烟、母亲妊娠早期感染史对NSCLP的发生具有交互作用;TGF-β3G15572-与母亲妊娠早期被动吸烟、母亲妊娠早期感染史、父亲知晓妊娠前吸烟、父亲知晓妊娠前饮酒、母亲妊娠早期补充维生素对NSCLP的发生具有交互作用.经Logistic回归验证,结果一致.结论 NSCLP是基因与环境因素共同作用的结果,易感基因多态性影响着个体对环境因素的反应,研究它们之间的相互关系对阐明NSCLP的病因及发病机制具有重要意义.     

Cephalometric outcome of two types of palatoplasty in complete unilateral cleft lip and palate

In complete unilateral cleft lip and palate (CLP), a vomerplasty is assumed to improve midfacial growth because of the reduction in scarring in the growth-sensitive areas of the palate. Our aim, therefore, was to evaluate maxillofacial morphology after a modified Langenbeck technique or a vomerplasty in children with complete unilateral CLP who were operated on by a single surgeon. As part of a one-stage closure of complete unilateral CLP done during the first year of life, the technique for repair of the hard palate repair differed between the two groups. In the modified group (n = 37, mean age 11 years) a modified von Langenbeck technique was used that resulted in denudation of the bony surface on the non-cleft side only. In the vomerplasty group (n = 37, mean age 11 years) a vomerplasty was used to cover the palatal bone. Lateral cephalograms from both groups were compared using the Eurocleft protocol. Fourteen angular variables were measured and 2 ratios calculated. Skeletal morphology in the groups was comparable. Maxillary incisor inclination (ILs/NL angle) and interincisal angle (ILs/ILi) were better after vomerplasty (p = 0.001 and 0.04, respectively) but soft tissue facial convexity (gs-prn-pgs) was less good after vomerplasty (p = 0.009). However, there was no difference between the groups in the other variable that reflected facial convexity (gs-sn-pgs) (p = 0.22). Modification of the palatoplasty had a limited effect on skeletal morphology in preadolescent children, but it resulted in better inclination of the maxillary incisors.     

A two-centre study on facial morphology in patients with complete bilateral cleft lip and palate at nine years of age

The aim of this study was to compare craniofacial morphology and soft tissue profiles in patients with complete bilateral cleft lip and palate at 9 years of age, treated in two European cleft centres with delayed hard palate closure but different treatment protocols. The cephalometric data of 83 consecutively treated patients were compared (Gothenburg, N = 44; Nijmegen, N = 39). In total, 18 hard tissue and 10 soft tissue landmarks were digitized by one operator. To determine the intra-observer reliability 20 cephalograms were digitized twice with a monthly interval. Paired t-test, Pearson correlation coefficients and multiple regression models were applied for statistical analysis. Hard and soft tissue data were superimposed using the Generalized Procrustes Analysis. In Nijmegen, the maxilla was protrusive for hard and soft tissue values (P = 0.001, P = 0.030, respectively) and the maxillary incisors were retroclined (P < 0.001), influencing the nasolabial angle, which was increased in comparison with Gothenburg (P = 0.004). In conclusion, both centres showed a favourable craniofacial form at 9-10 years of age, although there were significant differences in the maxillary prominence, the incisor inclination and soft tissue cephalometric values. Follow-up of these patients until facial growth has ceased, may elucidate components for outcome improvement.     

Nasolabial and alveolar morphology following presurgical orthopaedic treatment in complete unilateral clefts of lip, alveolus and palate

INTRODUCTION: The purpose of this study was to assess the three-dimensional (3-D) facial and alveolar morphology of patients with unilateral clefts of lip, alveolus and palate by means of a computer-aided diagnosis system. PATIENTS AND METHODS: Maxillary orthopaedic treatment was performed using soft/hard acrylic plates (Hotz's) within 2 weeks of birth. The nasolabial and alveolar morphology of 15 patients was evaluated before orthopaedic treatment (2 weeks of age) and before cheiloplasty (3 months of age). Nasolabial form was measured using a 3-D optical scanner. Twenty-one landmarks were extracted from the data and analysed linearly and angularly. Alveolar forms were measured with a high-accuracy contact-type 3-D digitizer on plaster casts. Seven landmarks were digitized and analysed linearly and angularly. RESULTS: Some growth was observed in the intercanthal distance, alar width, intercommissural width, and height of the lip. There was little change in the width of the cleft lip or displacement of the columella base, while the alveolar cleft narrowed. CONCLUSION: Presurgical orthopaedics reduces cleft width and makes subsequent surgery easier.